Martin Horák

Cortical Thickness Mapping to Identify Focal Osteoporosis in Patients with Hip Fracture

Background Individuals with osteoporosis are predisposed to hip fracture during trips, stumbles or falls, but half of all hip fractures occur in those without generalised osteoporosis. By analysing ordinary clinical CT scans using a novel cortical thickness mapping technique, we discovered patches of markedly thinner bone at fracture-prone regions in the femurs of women with acute hip fracture compared with controls. Methods We analysed CT scans from 75 female volunteers with acute fracture and 75 age- and sex-matched controls. We classified the fracture location as femoral neck or trochanteric before creating bone thickness maps of the outer ‘cortical’ shell of the intact contra-lateral hip. After registration of each bone to an average femur shape and statistical parametric mapping, we were able to visualise and quantify statistically significant foci of thinner cortical bone associated with each fracture type, assuming good symmetry of bone structure between the intact and fractured hip. The technique allowed us to pinpoint systematic differences and display the results on a 3D average femur shape model. Findings The cortex was generally thinner in femoral neck fracture cases than controls. More striking were several discrete patches of statistically significant thinner bone of up to 30%, which coincided with common sites of fracture initiation (femoral neck or trochanteric). Interpretation Femoral neck fracture patients had a thumbnail-sized patch of focal osteoporosis at the upper head-neck junction. This region coincided with a weak part of the femur, prone to both spontaneous ‘tensile’ fractures of the femoral neck, and as a site of crack initiation when falling sideways. Current hip fracture prevention strategies are based on case finding: they involve clinical risk factor estimation to determine the need for single-plane bone density measurement within a standard region of interest (ROI) of the femoral neck. The precise sites of focal osteoporosis that we have identified are overlooked by current 2D bone densitometry methods.

Focal osteoporosis defects play a key role in hip fracture.

Background Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. Methods The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location (‘femoral neck’ or ‘trochanteric’) to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. Results Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. Conclusion Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.

Changes in the sexual dimorphism of the human mandible during the last 1200 years in Central Europe.

According to many investigations, changes in mandibular morphology can occur synchronously with changes in the environment, and sexual dimorphism of the mandible can be influenced by the environment. Sexual dimorphism during the last 1200 years was evaluated using geometric morphometric analysis of virtual cranial models. The method of geometric morphometrics allows differences in size and shape to be assessed separately. We analyzed groups of adult individuals dating to Early Middle Ages, High Middle Ages, Early Modern Ages and from a modern Czech population (21st century). Significant sexual dimorphism in mandibular size was found in all populations. A trend in the sexual dimorphism of size was seen, with differences between the sexes increasing gradually over time. Size changes in female mandibles were a better reflection of environmental conditions and climate than size changes in male mandibles. Regarding changes in the sexual dimorphism of shape, significant dimorphism was found in all four samples. However, the pattern of mandibular shape dimorphism was different and varied considerably between samples. There was only one stable shape trait showing sexual dimorphism across all four samples in our study: the gonion lies more laterally in male than in female mandibles and male mandibles are relatively wider than female mandibles. Sexual dimorphism of shape is not influenced by the climate; instead sexual selection might play a role. This research supports earlier studies that have found that the degree and pattern of sexual dimorphism is population-specific and the factors regulating sexual dimorphism today may not be the same as those in the past.

Computed Tomographic Angiography in Proximal Femoral Focal Deficiency

BACKGROUND Because there is limited information concerning the vascular pattern and the role of vessels in patients with proximal femoral focal deficiency, the vascular supply of the lower extremities was studied systematically with use of computed tomographic angiography in order to identify vascular changes, relate any vascular changes to the classification of the deficiency, and establish that there are no major changes in the topographical anatomy of the vessels. METHODS Standardized computed tomographic techniques were used in twenty-one patients (thirteen boys and eight girls who ranged from one to nineteen years old) with proximal femoral focal deficiency types I through IV and VII, VIII, and IX, according to the Pappas classification. RESULTS A common anatomical vascular pattern, in which the hypoplastic extremity was supplied through the femoral artery, was detected in nineteen patients. In patients with Pappas type-I through IV disease, the external iliac, femoral, and deep femoral arteries were substantially reduced in length and diameter and the deep femoral artery arose more proximally in comparison with that in the contralateral extremity; however, in the patients with Pappas type-VII, VIII, or IX disease, the diameters of the arteries and the origin of the deep femoral artery were similar to those of the contralateral extremity. In two patients with Pappas type-III disease, atypical anatomy of the vessels was found. The anterior part of the thigh and the pseudarthrosis were supplied through the femoral artery (the external iliac artery) as a terminal branch, while the remainder of the extremity was supplied from the internal iliac artery, which entered the thigh posterior to the hip as the inferior gluteal artery and continued as the artery to the sciatic nerve to the popliteal artery. No substantial anastomoses were found between the femoral and the posterior arteries in these vascular patterns. CONCLUSIONS Computed tomographic-angiographic reconstruction can be used to depict the spatial configuration of the pseudarthrosis and the vascular pattern of the extremity in patients with proximal femoral focal deficiency. We found distinct vascular changes in the majority of the involved thighs, but there were no typical changes related to the Pappas classification. Because we found atypical vascular patterns in two patients, evaluation of the vessels with use of various diagnostic methods is recommended in patients with severe types of proximal femoral focal deficiency.

Distribution of chondrocytes containing alpha-smooth muscle actin in human normal, osteoarthrotic, and transplanted articular cartilage

The aim of our study was to evaluate the occurrence of chondrocytes containing alpha-smooth muscle actin in human normal and diseased cartilage. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, S-100 protein, CD 34, and desmin was performed on samples of human articular cartilage obtained at autopsy following sudden death, during total hip and knee replacement for osteoarthritis, or after femoral neck fracture in patients without symptoms of osteoarthritis. Moreover, the layers of residual cartilage from chondral posttraumatic defects obtained during preoperative arthroscopy and of newly formed cartilage after autologous-chondrocyte transplantation (Hyalograft C) obtained during second-look arthroscopy were also examined by immunohistochemistry and RT PCR. Our study showed that a significant percentage of articular chondrocytes express alpha-smooth muscle actin in healthy, diseased, and regenerated articular cartilage. Alpha-actin positive chondrocytes (18%) were observed predominantly in the upper zone of normal articular cartilage. By contrast, only approximately 10% of cartilage cells in the deep region stained for this contractile actin isoform. Actin-positive chondrocytes (myochondrocytes) are formed predominantly in response to injury to the osteoarthrotic cartilage, at sites of defective healing, and in newly formed cartilage after autologous chondrocyte transplantation. Fibrocartilage is present in some of these conditions, and it is known that this tissue contains chondrocytes with actin. The presence of myochondrocytes in the surface layer of normal articular cartilage indicates that this region probably plays an important role in maintaining cartilage integrity. Myochondrocytes may utilize the contractile actin isoform in manipulating the extracellular matrix of articular cartilage. It is also possible that actin-containing chondrocytes have a higher potential for regeneration in contrast to chondrocytes that do not contain this contractile material in their cytoplasm.

Rich table but short life : diffuse idiopathic skeletal hyperostosis in Danish astronomer Tycho Brahe (1546-1601) and its possible consequences.

The exhumation of Danish astronomer Tycho Brahe (1546–1601) was performed in 2010 to verify speculative views on the cause of his death. Previous analyses of skeletal and hair remains recovered from his grave refuted the presumption that he died from poisoning. These studies also outlined the possibility that he actually died from an acute illness, echoing the rather vague and inaccurate testimony of some historical records. We performed a detailed paleopathological analysis of Tycho Brahe’s skeletal remains, along with a reconstruction of his diet based on carbon and nitrogen stable isotopes analysis and an estimate of his physical status (relative body fat) based on medullar and cortical dimensions of the femoral shaft. The astronomer’s remains exhibit bone changes indicative of diffuse idiopathic skeletal hyperostosis (DISH). The study further allows us to classify him as obese (100% reliability according to our decision tree designed from Danish males), and points out his rich diet (high input of animal protein and/or marine resources) and high social status. Comorbidities of DISH and obesity are reviewed, and their influence on health status is discussed. We further consider some conditions associated with metabolic syndrome as possible causes of Tycho Brahe’s final symptoms (urinary retention, renal failure and coma), including diabetes, alcoholic ketoacidosis and benign prostatic hypertrophy. Although a definite and specific diagnosis cannot be established, our study points to today’s civilization diseases often associated with DISH and metabolic syndrome as the possible cause of death of Tycho Brahe.

Exercise-induced circulating microRNA changes in athletes in various training scenarios

Background The aim of the study was to compare selected extracellular miRNA levels (miR-16, miR-21, miR-93 and miR-222 with the response to 8-week-long explosive strength training (EXPL), hypertrophic strength training (HYP) and high-intensity interval training (HIIT). Methods 30 young male athletes of white European origin (mean age: 22.5 ± 4.06 years) recruited at the Faculty of Sports Studies of Masaryk University were enrolled in this study. The study participants were randomly assigned to three possible training scenarios: EXPL, HYP or HITT and participated in 8-week-long program in given arm. Blood plasma samples were collected at the baseline and at week 5 and 8 and anthropometric and physical activity parameters were measured. Pre- and post-intervention characteristics were compared and participants were further evaluated as responders (RES) or non-responders (NRES). RES/NRES status was established for the following characteristics: 300°/s right leg extension (t300), 60°/s right leg extension (t60), isometric extension (IE), vertical jump, isometric extension of the right leg and body fat percentage (BFP). Results No differences in miRNA levels were apparent between the intervention groups at baseline. No statistically significant prediction role was observed using crude univariate stepwise regression model analysis where RES/NRES status for t300, t60, IE, vertical jump and pFM was used as a dependent variable and miR-21, miR-222, miR-16 and miR-93 levels at baseline were used as independent variables. The baseline levels of miR-93 expressed an independent prediction role for responder status based on isometric extension of the right leg (beta estimate 0.76, 95% CI: -0.01; 1.53, p = 0.052). Discussion The results of the study indicate that 8-week-long explosive strength training, hypertrophic strength training and high-intensity interval training regimens are associated with significant changes in miR-16, mir-21, miR-222 and miR-93 levels compared to a baseline in athletic young men.

Facial approximation of Tycho Brahe’s partial skull based on estimated data with TIVMI-AFA3D

The virtual approach in physical and forensic anthropology is increasingly used to further analyze human remains, but also to propose new didactic means for visualization and dissemination of scientific results. Computerized facial approximation (FA) offers an alternative to manual methods, but usually requires a complete facial skeleton to allow for the estimation of the facial appearance of an individual. This paper presents the case of Tycho Brahe, Danish astronomer born during the XVIth century, whose remains were reanalyzed at the occasion of a short exhumation in 2010. Cranial remains of Brahe were poorly preserved, with only a partial facial skeleton, and virtual anthropology tools were used to estimate the missing parts of his skull. This 3D restoration was followed by a FA using TIVMI-AFA3D, subsequently textured with graphic tools. The result provided an interesting estimate that was compared with portraits of the astronomer. The impact of the missing data estimation was investigated by performing FAs on 10 complete test subjects and the same 10 subjects after cropping and estimating 50% of the landmarks (reproducing the preservation state of Tycho Brahes cranial remains). The comparison between the FA based on the complete and incomplete skulls of the same subject produced a visual assessment of the estimation impact on FAs which is relatively low. This procedure is an alternative to manual methods and offers a reproducible estimate of a face based on incomplete cranial remains. Although the case report concerns a historical individual, the robust automatic estimation of missing landmarks followed by a FA has value for forensic caseworks as a support to the identification process.